PARENCHYMAL AND NONPARENCHYMAL UPTAKE OF TC-99M, IN-111, AND I-125 LOW-DENSITY-LIPOPROTEIN IN THE NORMAL AND ESTRADIOL-STIMULATED RAT-LIVER- TRACER VALIDATION FOR QUANTITATIVE LOW-DENSITY-LIPOPROTEIN SCINTIGRAPHY

This study quantifies the parenchymal and nonparenchymal uptake of tec hnetium-99m (Tc-99m)- and indium-111 (In-111)-low-density Lipoprotein (LDL) in different states of hepatic LDL-receptor activity to validate quantitative LDL scintigraphy. Iodine-125 (I-125)-LDL was used as ref erence tracer. Four Sprague-Dawley rats with 17-alpha-ethinyl estradio l (EE)-stimulated LDL-receptor activity and five controls received all three tracers simultaneously 90 minutes before collagenase liver perf usion and metrizamide gradient cell separation. Total liver uptake of Tc-99m-, In-111-, and I-125-LDL was 1.8 +/- 1.0, 1.6 +/- 0.8, and 0.2 +/- 0.2% injected dose/g organ weight, respectively. The contribution of nonparenchymal cells to total hepatic tracer uptake was 5.4 +/- 4.7 %, 11.6 +/- 10.3%, and 9.6 +/- 7.6% in controls. Estradiol treatment i ncreased total liver uptake to 2.4 +/- 0.5, 2.0 +/- 0.2, and 0.5 +/- 0 .3% injected dose/g and reduced nonparenchymal cell contribution to 2. 3 +/- 2.6%, 4.2 +/- 4.8%, and 2.6 +/- 2.9%, respectively. Dual-isotope scintigraphy in EE-treated and control rats confirmed these data, wit h a lower total hepatic uptake of In-111-LDL in comparison with Tc-99m -LDL but a comparative degree of increase by EE treatment. Both behave quantitatively comparable as residualizing tracers, yet Tc-99m-LDL sh ows a higher affinity to the LDL receptor pathway of parenchymal cells . However, the nonspecific uptake of both tracers can be neglected for quantitative LDL scintigraphy, and external imaging of hepatic tracer uptake primarily reflects LDL-receptor activity of parenchymal cells.